Pan coating processes are routinely used to apply coating to tablets. Typically, a batch of tablets is loaded into a drum (referred to herein as a pan) and a liquid solution, dispersion, or suspension containing coating material (referred to herein as coating solution) is applied to the tablets as the pan rotates in order to coat the tablets. In the pharmaceutical industry, the pan is typically perforated and, thus, the pan is commonly referred to as a perforated pan. The coating uniformity of the tablets is based on a number of variables such as the design of the pan, pan rotation speed, baffle design within the pan, number of tablets, tablet size, tablet shape, and atomization and distribution of the coating solution. Coating uniformity among the tablets being coated is a fundamental goal of the coating process. Due to the complexity of atomization and distribution of the coating solution, tablet circulation patterns, and processing variables associated with the coating process, it is difficult to accurately predict coating uniformity.
Uniformity of coating from tablet-to-tablet (referred to herein as “coating uniformity”) is desirable in coating processes and is essential for drug layering (i.e., coating active pharmaceutical ingredients onto tablets). Coating uniformity for a pan coating process may be examined experimentally using test batches of tablets. In this approach, a test batch of tablets is loaded into the pan of a pan coating apparatus. The test batch is then coated for a predetermined period of time. Coated tablets within the test batch are sampled at various times to determine if the level of coating uniformity among the sampled tablets is acceptable. If the level of coating uniformity is unacceptable, the process is repeated using another test batch of tablets. All test batches are typically discarded.
Typically, tablets and coating solutions that will be used during production are also used during testing. The tablets often include expensive pharmaceutical drugs. In addition, the coating solution may include expensive pharmaceutical drugs as well. Accordingly, discarding test batches including these drugs is expensive.
Additionally, the test batches (which may be manufactured in actual production equipment or pilot/lab-scale equipment) typically include fewer tablets than a production batch of tablets being coated for market distribution. Therefore, the results obtained from the test batches are extrapolated to predict coating uniformity for the number of tablets in the production batches. Existing techniques for extrapolating test batch data to predict coating uniformity for production batches are imprecise, which leads to discrepancies between the predicted coating uniformity and the actual coating uniformity of the production batches. If the discrepancy is too great for a particular production batch, that batch is discarded and the pan coating process is modified. The pan coating process may need several modifications to obtain an acceptable production batch of tablets.
The use of production tablets and coating solutions during testing and the amount of time required for testing and modifying the pan coating process for production contribute to the total costs associated with the production of coated tablets. Additionally, the amount of time required for testing delays entry of the production tablets into the market place, where each day of delay potentially results in a large amount of lost revenue. There is an ever present desire to reduce costs associated with the production of coated tablets and to reduce the amount of time needed to introduce production tablets to the market place. Accordingly, methods and computer program products for determining coating uniformity that are not subject to these limitations are needed. The present invention addresses this need among others.